Previous investigations in our laboratory have shown that when iodine-125, which emits electrons with energies of less than 25 keV, is affixed to the DNA of dividing cells only 3-6 disintegrations (or less than 1 rad) deposited in the nucleus are necessary to result in replication failure. This compares with A Do of 170R for x-ray exposure. Further experiments are now designed in two areas. First, this toxicity will be substantiated further in cultured mammalian cells by investigating the effects of iodine-135, incorporated into DNA as the thymidine analog iododeoxyuridine (IUdR), on division delay in both asynchronous and synchronized cultures. In addition, the production of single strand breaks will be measured by alkaline sucrose gradient centrifugation. Cytogenetic changes will be determined by labeling in mid S and scoring aberrations at the next mitotic interval. An attempt will also be made to determine the toxicity of iodine-125 when it is uniformly distributed through the cell. Other low energy electron emitting isotopes will be studied, using the same biological endpoints. Another area of investigation will be the potential therapeutic uses of IUdR 125. This will be tested by the perfusion of animal solid tumors and measuring survival, time-to-death, and tumor size. The therapeutic value of these electrons will also be determined in an ascites tumor system where cell replication can be correlated with the amount of IUdR 125 administered. Mortality, survival times and weight gain will be scored. The aim of these investigations will be to determine the toxicity of isotopes which emit low energy electrons and to utilize this information as a basis for cancer therapy.